Close link between CD4 and CD8 T cell proliferation defects in patients with human immunodeficiency virus disease and relationship to extended periods of CD4 lymphopenia

T cell proliferation failure is commonly associated with human immunodeficiency virus (HIV) infection. By examining T cell function on a single-cell basis, we found that CD4+ T cell prolifer-ation failure was often accompanied by CD8+ T cell proliferation defects in patients with HIV disease. The defects are characterized by a proportional failure and reduced efficiency of pre-cursor T cell proliferation after stimulation. In this study, patients who historically had low levels of circulating CD4+ T cells were most likely to demonstrate cellular proliferation failure, regardless of current CD4+ T cell counts. In contrast, neither historical nor current plasma HIV RNA levels were predictive of proliferation failure. These results suggest that mechanisms of T cell prolifer-ation failure are more complex than can be explained by the direct effects of HIV replication and that therapeutic intervention to avoid prolonged periods of CD4+ lymphopenia may be de-sirable for the preservation of immune function in patients with HIV disease. Human immunodeficiency virus (HIV) infection is character-ized by progressive immunodeficiency. The functional immune impairments are broad-ranging and include defects not only in the principle target of HIV replication, CD4+ T cells [1–8], bu